[64Cu]FBP8 PET for Early Detection of Intracardiac Thrombus in Amyloid Cardiomyopathy

Overview

The primary goal of this pilot study is to determine whether \[64Cu\]FBP8, a novel fibrin-binding positron emission tomography (PET) probe, can identify intracardiac thrombi when paired with simultaneous hybrid cardiac PET/MRI in twenty (20) individuals with transthyretin or light chain cardiac amyloidosis and atrial fibrillation (AF) or atrial flutter (AF). The primary hypothesis of this study is that \[64Cu\]FBP8 PET/MRI can identify intracardiac thrombi in \>90% of subjects with confirmed intracardiac thrombi based on transesophageal echocardiogram (TEE). In secondary analyses, the investigators will seek to determine associations between intracardiac thrombi and left atrial function and left ventricular amyloid burden.

Detailed description

\[64Cu\]FBP8 is a novel copper-64 labeled molecular imaging probe that selectively binds to fibrin, the main constituent of human thrombi. In animal models, \[64Cu\]FBP8 has been shown to effectively detect pulmonary emboli, deep venous thromboses, and intracardiac thrombi. In a first-in-human study, \[64Cu\]FBP8 paired with simultaneous cardiac positron emission tomography (PET) and magnetic resonance imaging (MRI) accurately detected intracardiac thrombi (specifically, left atrial appendage \[LAA\] thrombi) in patients with atrial fibrillation (AF) with an accuracy of \>90% using transesophageal echocardiogram (TEE) as the reference standard. The investigators propose to study the value of \[64Cu\]FBP8 PET/MRI to detect intracardiac thrombi in patients with cardiac amyloidosis.

This pilot study is designed to assess the value of \[64Cu\]FBP8 PET/MRI to detect intracardiac thrombi in twenty (20) patients with cardiac amyloidosis and atrial fibrillation (AF) or atrial flutter (AFL) compared to TEE. The primary hypothesis is that \[64Cu\]FBP8 PET/MRI can identify intracardiac thrombi in \>90% of subjects with confirmed intracardiac thrombi based on TEE. In secondary analyses, the investigators will seek to determine associations between intracardiac thrombi and left atrial function and left ventricular amyloid burden.

Interventions

• Drug [64Cu]FBP8 PET/MR
  Simultaneous cardiac PET/MR images will be obtained following injection of \[64Cu\]FBP8.

Primary outcome measures

• Intracardiac Thrombus [Time frame: 1 day]

Eligibility criteria

Inclusion criteria

• Have the ability to give written informed consent;
• History of amyloid cardiomyopathy (ATTR-CM or AL-CM);
• History of AF or AFL;
• Retrospective enrollment: TEE to evaluate LAA within the previous 14 days, provided the anticoagulation regimen the patient is on is not changed after the TEE. If a patient has a negative TEE and continues the same stable anticoagulation regimen, then it is unlikely that a new thrombus will develop in the LAA within the next 14 days. Likewise, if a patient not taking any anticoagulation has a thrombus in the LAA, then it is unlikely that this thrombus will resolve spontaneously in the next 14 days if the patient remains off anticoagulation. If the TEE leads to a change being made in the anticoagulation regimen (started/stopped/dose modified), then a time window of 72 hours from the TEE to PET/MR imaging will be used. This scheme will ensure that the TEE can serve as an accurate gold standard;
• Prospective: TEE to evaluate LAA thrombus scheduled in upcoming 14 days;

Exclusion criteria

• Electrical implants such as cardiac pacemaker/defibrillator, perfusion pump, direct brain stimulator;
• Pregnancy or breastfeeding (a negative quantitative serum or urine hCG pregnancy test is required for females having child-bearing potential before the subject can participate);
• Claustrophobia;
• Subjects will be excluded if research-related radiation exposure exceeds current Radiology Department guidelines (i.e. 50 mSv in the prior 12 months);
• Unable to lie comfortably on a bed inside the PET/MR scanner;
• Subjects under direct or indirect (i.e., same department as PIs) supervision of the principal investigator;
• Body weight over the weight limit for the moving table (> 300 lbs for the MR table);
• Metallic or electric implants contraindicated for PET/MR scanning;
• Stroke, myocardial infarction, cardiac or major surgery within the last 3 months;
• History of LAA ligation/exclusion or presence of a LAA occlusion device;
• History of syncope within the last 6 weeks;
• Heart rate persistently >120 bpm or persistently <50 bpm;
• Daytime pauses >3 seconds;
• Lack of a prior transthoracic echocardiogram within the previous 6 months;
• Does not have the ability to give written informed consent;
• Determined by the investigator(s) to be clinically unsuitable for the study (e.g., based on screening visit and/or during study procedures);

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Diagnostic

Study locations

United States · 1 center

• Brigham and Women's Hospital — Boston

Publications

• Izquierdo-Garcia D, Desogere P, Philip AL, Mekkaoui C, Weiner RB, Catalano OA, Iris Chen YC, DeFaria Yeh D, Mansour M, Catana C, Caravan P, Sosnovik DE. Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance. JACC Cardiovasc Imaging. 2022 Mar;15(3):504-515. doi: 10.1016/j.jcmg.2021.08.009. Epub 2021 Oct 13. PMID 34656469
• Vilches S, Fontana M, Gonzalez-Lopez E, Mitrani L, Saturi G, Renju M, Griffin JM, Caponetti A, Gnanasampanthan S, De Los Santos J, Gagliardi C, Rivas A, Dominguez F, Longhi S, Rapezzi C, Maurer MS, Gillmore J, Garcia-Pavia P. Systemic embolism in amyloid transthyretin cardiomyopathy. Eur J Heart Fail. 2022 Aug;24(8):1387-1396. doi: 10.1002/ejhf.2566. Epub 2022 Jul 11. PMID 35650018
• Donnellan E, Hussain M, Marrouche N, Park M, Martin M, Hanna M, Wazni O, Collier P, Jaber W. Left Atrial Strain May Predict Thrombus Formation in Patients With Transthyretin Cardiac Amyloidosis. JACC Clin Electrophysiol. 2023 Aug;9(8 Pt 1):1418-1420. doi: 10.1016/j.jacep.2023.03.013. Epub 2023 May 24. No abstract available. PMID 37227355

Identifiers

NCT: NCT07560306 · 2025P003091

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗